Mosthaf L, Eriksson J, Häring H U, Groop L, Widen E, Ullrich A
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2633-5. doi: 10.1073/pnas.90.7.2633.
Skeletal muscle insulin resistance plays a pivotal role in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM), as individuals with this defect are at increased risk of developing the disease later in life. To assess whether the abnormal expression of the structurally distinct human insulin receptor isoforms, HIR-A and HIR-B, which has been found in skeletal muscle of NIDDM patients, is a feature of a prediabetic state, skeletal muscle biopsies from nondiabetic individuals ranging from high insulin sensitivity to insulin resistance were examined. Polymerase chain reaction analysis of mRNA from muscle biopsies detected exclusive or predominant expression of HIR-A in 13 patients with normal insulin sensitivity. In contrast, 7 subjects with various degrees of insulin resistance exhibited abnormally increased HIR-B RNA expression. This association suggests the abnormal expression of receptor isoforms as a characteristic of the prediabetic state and supports the notion of a connection of this aberration with the pathogenesis of NIDDM. Changes in HIR-A/B expression in the skeletal muscle may thus provide a prognostic criterion for the development of NIDDM.
骨骼肌胰岛素抵抗在非胰岛素依赖型糖尿病（NIDDM）的发病机制中起关键作用，因为有这种缺陷的个体在晚年患该病的风险增加。为了评估在NIDDM患者骨骼肌中发现的结构不同的人胰岛素受体亚型HIR - A和HIR - B的异常表达是否为糖尿病前期状态的一个特征，我们检查了从胰岛素敏感性高到胰岛素抵抗的非糖尿病个体的骨骼肌活检样本。对肌肉活检样本的mRNA进行聚合酶链反应分析发现，13名胰岛素敏感性正常的患者中HIR - A呈排他性或主要表达。相比之下，7名有不同程度胰岛素抵抗的受试者表现出HIR - B RNA表达异常增加。这种关联表明受体亚型的异常表达是糖尿病前期状态的一个特征，并支持这种异常与NIDDM发病机制相关的观点。因此，骨骼肌中HIR - A/B表达的变化可能为NIDDM的发展提供一个预后标准。
